Program Director/Principal Investigator (Last, First, Middle): '^^' Gregory O. PROJECT SUMMARY (See instmctions): The development of powerful new methods for the generation of carbon-carbon bonds has an impact on a wide array of disciplines that require the synthesis of organic compounds (e.g., biological chemistry, pharmaceutical chemistry, and biology); transition metals can catalyze carbon-carbon bond-forming processes, such as cross-couplings of organic electrophiles and nucleophiles, that would otherwise be difficult or impossible to achieve. Furthermore, because the two mirror-image isomers (enantiomers) of a molecule generally have different biological activity due to the handedness of the molecules of life (e.g., peptides, DNA, RNA, and carbohydrates), there is a need in the biomedical community to efficiently generate compounds in stereoisomerically pure form. This research program is directed at addressing both of these challenges. During the next grant period, a largely unexplored dimension of cross-coupling reactions will be investigated: processes that employ alkyl electrophiles as substrates. Efforts will focus on the development of versatile catalysts, including chiral catalysts, for a wide range of powerful bond-forming processes. Such reactions have the potential to simultaneously generate a carbon-carbon bond and to define up to two new stereocenters. Mechanistic studies will play an important role in this project, since an improved understanding of metal-based reactivity will facilitate catalyst development. This research program offers an opportunity to have a substantial impact on synthetic chemistry, as well as to enrich our understanding of once-unexpected chemical reactivity. RELEVANCE (See instructions): The development of efficient new chemical processes will have a substantial impact on a wide array of biomedical disciplines that require the synthesis of organic compounds (e.g., biological chemistry, pharmaceutical chemistry, and biology). This project is focused on the discovery of new methods for the synthesis of carbon-carbon bonds (which form the backbone of organic molecules) and for the control of the chirality (handedness) of compounds, which can be central to biological activity.